Natural products provide a wide range of biologically active agents, many of which have unique profiles of pharmacological activity and therapeutic potential. Over two hundred alkaloids have been identified in extracts from amphibian skins. These included batrachotoxins, which are potent activators of sodium channels, histrionicotoxins, which are noncompetitive blockers of nicotinic receptor channel complexes and of potassium channels, and pumiliotoxins, which have myotonic and cardiotonic activity due to inhibitory effects on closing of sodium channels. Further alkaloids included new 2,5-disubstituted decahydroquinolines, 5,8-disubstituted indolizidines, 1,4-disubstituted quinolizidines, 3,5-disubstituted pyrrolizidines, pumiliotoxins, homopumiliotoxins and allopumiliotoxins, and tricyclic alkaloids, including pyrrolizidine oximes related to nitropolyzonamine a defensive alkaloid in millipedes, cyclopenta[b]quinolizidines, cocinellines identical to defensive alkaloids in ladybug beetles, and the potent noncompetitive blockers at muscle-type and ganglionic-type nicotinic receptor-channels. Characterization of alkaloids in non-dendrobatid amphibians indicated that the biosynthetic pathways to certain dendrobatid alkaloids have evolved separately in one lineage (genus) of amphibians from the families Bufonidae, Myobatrachidae and Ranidae and in a lineage leading to four genera in the family frogs remains an enigma although frogs raided in outside vivariums on wild-caught like compounds were detected in skin extracts, based on antagonism of radioligand binding, and have been partially characterized. Secretions of a tree frog used by Indians in hunting magic contained a unique peptide, which was named adenoregulin based on its stimulatory effects on binding of agonists to A1-adenosine receptors. Subdomains of an alkaloid-binding site were proposed to explain the interactions of batrachotoxins, aconitine and pumiliotoxin B at sodium channels.